In Parkinson’s Disease (PD) dopamine-producing-neurons gradually degenerate resulting in dopamine deficiency and in the main symptoms of PD. Current medications relieve symptoms by replenishing dopamine, but do not impede neurodegeneration and their chronic use causes serious side effects called dyskinesias. Current drug discovery efforts aim either at new symptomatic DA replacement treatments and alleviating dyskinesias, or towards stopping neurodegeneration.

Using synthetic chemistry, we designed the chemical compound BRF110 to activate the Nurr1:RXRα protein-complex which is involved in the development and function of dopamine neurons. BRF110 replenishes dopamine in PD mouse models and improves symptoms without inducing dyskinesias. Additionally, BRF110 prevents dopamine-producing-neuron loss which is caused by either PD causing toxins or PD associated mutations. Our findings indicate that dopamine production and neuroprotection are controlled by the Nurr1:RXRα protein-complex and point to a monotherapy approach for the treatment of PD.